Methyl (2S,4R)-1-[(3-cyanophenyl)sulfonyl]-4-(3,3-difluoropipendin-1-yl)pyrrolidine-2-carboxylate | 877406-60-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: Methyl (2S,4R)-1-[(3-cyanophenyl)sulfonyl]-4-(3,3-difluoropipendin-1-yl)pyrrolidine-2-carboxylate
• 英文别名: methyl (2S,4R)-1-(3-cyanophenyl)sulfonyl-4-(3,3-difluoropiperidin-1-yl)pyrrolidine-2-carboxylate
• CAS: 877406-60-5
• 化学式: C₁₈H₂₁F₂N₃O₄S
• 分子量: 413.445
• InChiKey: ULWNURWKNDBMCF-ZBFHGGJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  99.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Methyl (2S,4R)-1-[(3-cyanophenyl)sulfonyl]-4-(3,3-difluoropipendin-1-yl)pyrrolidine-2-carboxylate 在 水 、 lithium hydroxide 作用下， 以 乙腈 为溶剂， 生成 (2S,4R)-1-(3-cyanophenyl)sulfonyl-4-(3,3-difluoropiperidin-1-yl)pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of N-{N-[(3-cyanobenzene) sulfonyl]-4(R)-(3,3-difluoropiperidin-1-yl)-(l)-prolyl}-4-[(3′,5′-dichloro-isonicotinoyl) amino]-(l)-phenylalanine (MK-0617), a highly potent and orally active VLA-4 antagonist

  摘要：

  A series of prolyl-N-isonicotinoyl-(L)-4-aminophenylalanine derivatives substituted at the proline 4-position with cyclic amines was evaluated as VLA-4 antagonists. The ring size and presence or absence of fluorine affected potency and receptor occupancy. The analog with 3,3-difluoropiperidine at the proline 4-position (13) was the most potent compound and had very good duration of receptor occupancy in vitro. The ethyl ester prodrug of 13 demonstrated excellent receptor occupancy after oral dosing in rats. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.111
• 作为产物：
  描述：

  、 3,3-二氟哌啶 在 N,N-二异丙基乙胺 作用下， 反应 12.0h， 生成 Methyl (2S,4R)-1-[(3-cyanophenyl)sulfonyl]-4-(3,3-difluoropipendin-1-yl)pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Discovery of N-{N-[(3-cyanobenzene) sulfonyl]-4(R)-(3,3-difluoropiperidin-1-yl)-(l)-prolyl}-4-[(3′,5′-dichloro-isonicotinoyl) amino]-(l)-phenylalanine (MK-0617), a highly potent and orally active VLA-4 antagonist

  摘要：

  A series of prolyl-N-isonicotinoyl-(L)-4-aminophenylalanine derivatives substituted at the proline 4-position with cyclic amines was evaluated as VLA-4 antagonists. The ring size and presence or absence of fluorine affected potency and receptor occupancy. The analog with 3,3-difluoropiperidine at the proline 4-position (13) was the most potent compound and had very good duration of receptor occupancy in vitro. The ethyl ester prodrug of 13 demonstrated excellent receptor occupancy after oral dosing in rats. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.07.111

文献信息

• Vla-R Antagonists
  申请人：Chen Weichao

  公开号：US20070219252A1

  公开（公告）日：2007-09-20

  Compounds of Formula (I) are antagonists of VLA-4, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of inflammatory bowel disease including ulcerative colitis and Crohn's disease, multiple sclerosis, asthma, and rheumatoid arthritis.

  公式（I）的化合物是VLA-4的拮抗剂，因此可用于抑制或预防细胞黏附和细胞黏附介导的病理过程。这些化合物可以制成药物组合物，并适用于治疗炎症性肠病，包括溃疡性结肠炎和克罗恩病、多发性硬化症、哮喘和类风湿性关节炎。
• VLA-4 antagonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07776891B2

  公开（公告）日：2010-08-17

  Compounds of Formula (I) are antagonists of VLA-4, and as such are useful in the inhibition or prevention of cell adhesion and cell-adhesion mediated pathologies. These compounds may be formulated into pharmaceutical compositions and are suitable for use in the treatment of inflammatory bowel disease including ulcerative colitis and Crohn's disease, multiple sclerosis, asthma, and rheumatoid arthritis.

  式(I)的化合物是VLA-4的拮抗剂，因此在抑制或预防细胞黏附和细胞黏附介导的病理过程方面非常有用。这些化合物可以制成药物组合物，并适用于治疗炎症性肠病，包括溃疡性结肠炎和克罗恩病，多发性硬化症，哮喘和类风湿性关节炎。
• Discovery of N-{N-[(3-cyanobenzene) sulfonyl]-4(R)-(3,3-difluoropiperidin-1-yl)-(l)-prolyl}-4-[(3′,5′-dichloro-isonicotinoyl) amino]-(l)-phenylalanine (MK-0617), a highly potent and orally active VLA-4 antagonist
  作者：Shankar Venkatraman、Alec D. Lebsack、Kenneth Alves、Michael F. Gardner、Joyce James、Russell B. Lingham、Salony Maniar、Richard A. Mumford、Qian Si、Nicholas Stock、Kelly M. Treonze、Bowei Wang、Jasmine Zunic、Benito Munoz

  DOI：10.1016/j.bmcl.2009.07.111

  日期：2009.10

  A series of prolyl-N-isonicotinoyl-(L)-4-aminophenylalanine derivatives substituted at the proline 4-position with cyclic amines was evaluated as VLA-4 antagonists. The ring size and presence or absence of fluorine affected potency and receptor occupancy. The analog with 3,3-difluoropiperidine at the proline 4-position (13) was the most potent compound and had very good duration of receptor occupancy in vitro. The ethyl ester prodrug of 13 demonstrated excellent receptor occupancy after oral dosing in rats. (C) 2009 Elsevier Ltd. All rights reserved.